Certain organophosphorus (OP) compounds produce a delayed degeneration of neurons in susceptible species such as man and certain fowl. Some species, including the rat, are higly resistant to OP neuropathy. In the hen, the initial biochemical event in the neuropathy is inhibition of an enzyme, neurotoxic esterase (NTE), in nervous tissue. This enzyme has no known physiological function and very little is known of its distribution in nature. To better understand its role in toxic neuropathies, the occurrence of NTE in brain and other tissues of the hen and other animal species will be investigated. NTE will be determined by differential assay of phenyl valerate hydrolysis using paraoxon and mipafox as non-neurotoxic and neurotoxic inhibitors, respectively. An electrophoretic analysis of NTE will also be developed to help distinguish differences between enzyme from susceptible and non-susceptible species. Techniques for purifying and isolating NTE will be developed utilizing centrifugal subcellular fractionation, solvent and detergent solubilization, partitioning in aqueous multiphase polymer systems, and gel filtrations. Antibodies or activated lymphocytes will be raised against purified native and phosphorylated NTE for use in localization and in testing the immune hypothesis of OP neuropathy. A key hypothesis is to be tested is that NTE is a receptor protein for endogenous protein kinase. Neurotoxic OP esters are expected to block kinase-catalyzed phosphorylation of specific membrane proteins by gamma-(23P)-ATP. The long-range objective of this research is to understand how phosphorylation of NTE leads to degeneration of nervous tissue. It is hoped that detailed knowledge of the toxic response may shed light on the physiological function of NTE and perhaps be useful in understanding certain spontaneous diseases of the nervous system.